Mass General - Division of Clinical Research

A Study Evaluating the Efficacy and Safety of Giredestrant Combined With Palbociclib Compared With Letrozole Combined With Palbociclib in Participants With Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer (persevERA Breast Cancer)

Purpose

This Phase III, randomized, double-blind, placebo-controlled, multicenter study will evaluate the efficacy and safety of giredestrant combined with palbociclib compared with letrozole combined with palbociclib in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative locally advanced (recurrent or progressed) or metastatic breast cancer.

Condition

Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer

Eligibility

Eligible Ages: Over 18 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

Inclusion Criteria

For women who are premenopausal or perimenopausal and for men: treatment with approved LHRH agonist therapy for the duration of study treatment - Locally advanced (recurrent or progressed) or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent - Documented ER-positive tumor and HER2-negative tumor, assessed locally - Patients who have bilateral breast cancers which are both ER-positive and HER2-negative can be included in the study because the metastases are suitably targeted by the study treatments. If patients have bilateral tumors which are of different biomarker status, then proof of the ER and HER2 status of the metastases is required for study entry - No history of systemic anti-cancer therapy for locally advanced (recurrent or progressed) or metastatic disease - Disease recurrence from early-stage breast cancer after standard adjuvant endocrine therapy meeting the protocol-defined criteria of having received at least 24 months of treatment without disease progression during treatment and a disease-free interval since the completion of treatment that was greater than 12 months - Measurable disease as defined per RECIST v.1.1 or bone only disease which must have at least one predominantly lytic bone lesion confirmed by CT or MRI which can be followed - Eastern Cooperative Oncology Group Performance Status 0-1 - Adequate organ function

Exclusion Criteria

Disease recurrence during or within 12 months of completing prior neoadjuvant or adjuvant treatment with any CDK4/6 inhibitor - Prior treatment with a selective estrogen receptor degrader (SERD) - Treatment with any investigational therapy within 28 days prior to study treatment - Treatment with strong CYP3A inhibitors or inducers within 14 days or 5 drug elimination half-lives (whichever is longer) prior to randomization - Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term - Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease - Active cardiac disease or history of cardiac dysfunction, as defined in the protocol - Pregnant or breastfeeding

Study Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: Double (Participant, Investigator)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Giredestrant + Letrozole-matched Placebo + Palbociclib		Drug: Giredestrant Giredestrant is taken orally once per day on Days 1-28 of each 28-day treatment cycle. Other names: GDC-9545 RO7197597 RG6171 Drug: Letrozole-matched Placebo Letrozole-matched placebo is taken orally once per day on Days 1-28 of each 28-day treatment cycle. Drug: Palbociclib Palbociclib 125 mg is taken orally once per day on Days 1-21 of each 28-day treatment cycle. Drug: LHRH Agonist Only premenopausal/perimenopausal and male participants will receive a luteinizing hormone-releasing hormone (LHRH) agonist on Day 1 of each 28-day treatment cycle. The investigator will determine and supply the appropriate LHRH agonist locally approved for use in breast cancer.
Active Comparator Letrozole + Giredestrant-matched Placebo + Palbociclib		Drug: Giredestrant-matched Placebo Giredestrant-matched placebo is taken orally once per day on Days 1-28 of each 28-day treatment cycle. Drug: Letrozole Letrozole 2.5 milligrams (mg) is taken orally once per day on Days 1-28 of each 28-day treatment cycle. Drug: Palbociclib Palbociclib 125 mg is taken orally once per day on Days 1-21 of each 28-day treatment cycle. Drug: LHRH Agonist Only premenopausal/perimenopausal and male participants will receive a luteinizing hormone-releasing hormone (LHRH) agonist on Day 1 of each 28-day treatment cycle. The investigator will determine and supply the appropriate LHRH agonist locally approved for use in breast cancer.

More Details

Status: Active, not recruiting
Sponsor: Hoffmann-La Roche

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.